1. Field of the Invention
The present invention relates to the use of anti-inflammatory drugs for generation of a Th-1=IgG2a=CMI response for treatment of dermatological conditions.
2. Prior Art
Dissemination of the human papillomavirus has been found to be associated with suppression of cytokines and other factors leading to an ineffective Th-1 cell-mediated response. The regression of the human papillomavirus has been found to be associated with an increase in the expression of cytokines in a cell-mediated response. as well as a decrease in the viral load, and any markers associated with proliferation and differentiation. It is also recognized that Th-1 cells are involved in the induction of cellular immunity and this is characterized by a lower or absent antibody production. However, some Th-1 responses are associated with strong antibody production of IgG2a, IgG2b, and IgG3 subclasses. When a humoral response with strong antibody production does not develop. there is an incomplete cell-mediated response toward a pathogen. This explains the lack of humoral activities that is seen with the human papillomavirus.
Warts are produced by eruption of the underlying human papillomavirus (HPV). The development of warts is due to direct contact with virus particles. The risk of infection of warts depends not only the virulence of the virus particles, but also on the patient's susceptibility to viral attack and strength of the patient's immune system. Immunodeficient patients have greater susceptibility to infection. inadequate treatment for HPV, and frequent recurrences. Most standard therapies are ablative and caustic and treat only the visibly appearing warts and do not treat the underlying virus.
Certain quinolones have been reported as having some antiviral activity. In particular, ofloxacin, ciprofloxacin. and norfloxacin have been shown to inhibit HIV reverse transcriptase and a class of related quinolones are described in U.S. Pat. No. 5,217,972 as effective in the treatment or prevention of certain human and animal viral diseases. None of those indications however include HPV or warts.
Current treatments for genital warts include podophyllin, other acids, interferons, imiquimod, and other treatment mechanisms such as freezing, frying, cutting, boiling, burning, and topically applying immunomodulating measures to eradicate genital warts. This wide range of essentially destructive therapies and a few nondestructive therapies indicates that none have been found to be outstandingly effective. Most of these therapies have been used for years, and are painful for adults and not tolerated by children. Some can even result in scarring without demonstrating good long-term clinical results. The greater incidence of anogenital warts in the general population includes children. Children have very limited treatment options.
Optimum therapeutic strategy of anogenital infection would be a therapy that accelerates the induction of a strong virus specific immune response to effectuate wart regression with less pain and that could be well-tolerated by adults and children. This would lead to decreased viral persistence, recurrence, and transmission. Viral persistence in the form of visible warts are common and can eventually lead to anogenital neoplasia. The consequences of the lack of optimum therapy results in viral persistence in the form of warts. Warts are not just insignificant lesions, but can in the future lead to malignancies regardless of the immune status of the patient or HPV type. HPV genomes have been found in skin cancers and other types of cancers. Low risk types of HPV do not necessarily mean no risk for malignancies. High risk types of HPV and immunodeficiencies only create a greater predisposition leading to the process of malignant transformation. This phenomena of malignant transformation is frequently seen in immunocompromised patients and in viral persistence of high risk HPV types.
HPV is a systemic rather than just a localized skin manifestation. Untreated or recurrent anogenital warts can be transmitted not only sexually, but from an infected mother to her child. HPV has been found in the amniotic fluid from some pregnant women with cervical lesions. This very early transmission source as well as the presence of warts in the birth canal can lead to the development of life-threatening laryngeal papillomas. These may not develop at birth but can develop anytime during the first few years of a child's life. The median age being 3 years of age. There are also cases of newborns with anoTenitai warts present at birth or developing them in the first few years after birth. Autoinoculation and fomite transmission are other vehicles of non-sexual transmission of the genital human papillomavirus infection.
An optimum strategy for treatment of HPV would be in the form of a systemic immunomodulating medication with associated antiviral properties. It would not only impact a new form of therapy for existing warts, but could demonstrate effectiveness prophylactically. Prophylaxis could contribute immeasurably to less recurrence of warts and less transmission of this virus. Eradication of warts by whatever therapeutic measure that is employed only eliminates the visible presence of the genital papillomavinis, which are warts. It does not eliminate or address the underlying genital papillomavirus which leads to recurrences and transmission of this virus. Recurrences can occur during pregnancy or can be triggered by another virus or infection. States of immunocompromization created by conditions such as pregnancy, illness, stress, or infections are risk factors for wart recurrence. All patients with HPV will be vulnerable to recurrences for the rest of their lives.
Recurrences are even more common in immunodeficiencies. In immunodeficient patients and those with more virulent HPV types, viral persistence is a common occurrence. It is also associated with the frequent development of anogenital neoplasia. Anogenital neoplasia in immunosuppressed women persists, recurs, and extends to adjacent areas of the cervix, vagina, vulva, and anus.
Because of the lack of effective current therapy as well as the many aforementioned consequences of persisting anogenital warts, there is a critical need for the development of an optimum more effective therapy for genital papillomavirus infections.